JP2007121275A - Microchip and liquid mixing method and blood testing method using microchip - Google Patents

Microchip and liquid mixing method and blood testing method using microchip Download PDF

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JP2007121275A
JP2007121275A JP2006257568A JP2006257568A JP2007121275A JP 2007121275 A JP2007121275 A JP 2007121275A JP 2006257568 A JP2006257568 A JP 2006257568A JP 2006257568 A JP2006257568 A JP 2006257568A JP 2007121275 A JP2007121275 A JP 2007121275A
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flow path
microchip
liquids
cross
sectional area
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JP2007121275A5 (en
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Hiroshi Yo
博 楊
Yoshiki Sakaino
佳樹 境野
Hideyuki Karaki
英行 唐木
Akira Wakabayashi
彰 若林
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Fujifilm Corp
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Fujifilm Corp
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Priority to JP2006257568A priority Critical patent/JP2007121275A/en
Priority to EP06020279A priority patent/EP1767263A3/en
Priority to US11/527,698 priority patent/US20070077169A1/en
Publication of JP2007121275A publication Critical patent/JP2007121275A/en
Publication of JP2007121275A5 publication Critical patent/JP2007121275A5/ja
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
    • B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
    • B01F25/433—Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
    • B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
    • B01F25/433—Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
    • B01F25/4338—Mixers with a succession of converging-diverging cross-sections, i.e. undulating cross-section
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/65—Mixers with shaking, oscillating, or vibrating mechanisms the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchip capable of simply mixing constant amounts of two or more liquids having different ratios of viscosity coefficient / specific gravity / capacity; and to provide a mixing method using the microchip. <P>SOLUTION: The microchip comprises: a flow path substrate; an inlet port which is formed on the flow path substrate to introduce the two or more liquids; a flow path which is adapted to cause the two or more liquids introduced into the inlet port to flow while mixing them; and a decompression port which is configured to communicate with the flow path and to be connectable to a decompression means when reducing the pressure in the flow path. The flow path includes a first flow path portion and a second flow path portion provided so that they are alternately formed, wherein the first flow path portion has a cross-sectional area larger than that of another flow path in a direction in which the liquids flow, and the second flow path portion has a cross-sectional area smaller than that of the first flow path portion. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

本発明は、マイクロチップ、このマイクロチップを用いた混合方法及び血液検査方法に関する。   The present invention relates to a microchip, a mixing method using the microchip, and a blood test method.

従来、複数の液体を混合させる技術としては、例えば、下記特許文献１から３に示すものがある。   Conventional techniques for mixing a plurality of liquids include, for example, those shown in Patent Documents 1 to 3 below.

特開２００１−１２０９７２号公報JP 2001-120972 A 特開２００２−３４６３５５号公報JP 2002-346355 A 特開２００３−１０７７号公報JP 2003-1077 A

しかし、上記特許文献１から３に記載の方法は、粘度・比重・容量比が異なる２液を混合するには適さない。また、連続的な送液による混合であり、一定量（連続的な混合ではなく、ある一定量。例えば合計20μL）を混合するという使用目的には適さない。例えば、血液検査において、微小量の血液と希釈液とを混合させる場合には、上記の方法では均一に混合することができない。   However, the methods described in Patent Documents 1 to 3 are not suitable for mixing two liquids having different viscosities / specific gravity / volume ratios. Moreover, it is mixing by continuous liquid feeding, and is not suitable for the purpose of mixing a certain amount (a certain amount, not continuous mixing, for example, 20 μL in total). For example, in a blood test, when a very small amount of blood and a diluent are mixed, the above method cannot be mixed uniformly.

本発明は、上記事情に鑑みてなされたもので、その目的は、粘度・比重・容量比が異なる一定量の複数の液体を簡便に混合することができるマイクロチップ、そのマイクロチップを用いた混合方法を提供することにある。   The present invention has been made in view of the above circumstances, and the purpose thereof is a microchip capable of easily mixing a plurality of liquids having different viscosities / specific gravity / volume ratios, and mixing using the microchip. It is to provide a method.

本発明の上記目的は、下記によって達成される。
（１） 流路基板と、前記流路基板に形成され、複数の液体を導入するための投入ポートと、前記投入ポートに導入された前記複数の液体を混合させつつ流動させる流路と、前記流路に連通し、該流路内の雰囲気を減圧する際に、減圧手段が接続可能な減圧ポートとを備え、前記流路には、前記液体が流動する方向の断面積が他の流路における断面積に比して大きい第１流路部と、前記第１流路部より断面積が小さい第２流路部とが交互に形成されていることを特徴とするマイクロチップ。
（２） 前記第１流路部の断面積が前記第２の流路部の断面積に対して２倍以上であることを特徴とする上記（１）に記載のマイクロチップ。
（３） 前記第１流路部の容積が前記複数の液体全体の体積の８０％以上であることを特徴とする上記（１）又は（２）に記載のマイクロチップ。
（４） 前記第１流路部における前記液体の流れる方向に平行な方向の長さが、前記第２流路部における前記液体の流れる方向に平行な方向の長さに対して０．１〜１０倍であることを特徴とする上記（１）から（３）のいずれか１つに記載のマイクロチップ。
（５） 前記流路の底面の角部が流路幅の１０％以上の曲率半径を有することを特徴とする上記（１）から（４）のいずれか１つに記載のマイクロチップ。
（６） 前記投入ポートが１つであることを特徴とする上記（１）から（５）のいずれか１つに記載のマイクロチップ。
（７）
前記複数の液体が前記流路を往復移動することを特徴とする上記（１）から（６）のいずれか１つに記載のマイクロチップ。
（８） 上記（１）から（７）のいずれか１つに記載のマイクロチップを用いて複数の液体を混合することを特徴とする液体の混合方法。
（９） 前記複数の液体のうち少なくとも１種類の被混合液を投入ポートに予め入れておくことを特徴とする上記（８）に記載の液体の混合方法。
（１０） 上記（１）から（７）のいずれか１つに記載のマイクロチップを用いて血液と希釈液とを混合することを特徴とする血液検査方法。
（１１） 流路基板と、前記流路基板に形成され、複数の液体を導入するための投入ポートと、前記投入ポートに導入された前記複数の液体を混合させつつ流動させる流路とを備え、前記流路内の雰囲気を加圧する際に、前記投入ポートに加圧手段が接続可能であって、前記流路には、前記液体が流動する方向の断面積が他の流路における断面積に比して大きい第１流路部と、前記第１流路部より断面積が小さい第２流路部とが交互に形成されていることを特徴とするマイクロチップ。 The above object of the present invention is achieved by the following.
(1) a flow path substrate, an input port for introducing a plurality of liquids formed in the flow path substrate, a flow path for allowing the plurality of liquids introduced into the input port to flow while mixing, A pressure reducing port that communicates with the flow path and to which a pressure reducing means can be connected when depressurizing the atmosphere in the flow path, and the flow path has a cross-sectional area in the direction in which the liquid flows. A microchip, wherein a first flow path portion having a cross-sectional area larger than the first flow path portion and a second flow path portion having a cross-sectional area smaller than that of the first flow path portion are alternately formed.
(2) The microchip according to (1), wherein a cross-sectional area of the first flow path portion is twice or more a cross-sectional area of the second flow path portion.
(3) The microchip as described in (1) or (2) above, wherein the volume of the first flow path portion is 80% or more of the volume of the whole of the plurality of liquids.
(4) The length of the first flow path portion in the direction parallel to the liquid flow direction is 0.1 to the length of the second flow path portion in the direction parallel to the liquid flow direction. The microchip according to any one of (1) to (3) above, which is 10 times.
(5) The microchip according to any one of (1) to (4), wherein a corner portion of a bottom surface of the flow path has a curvature radius of 10% or more of a flow path width.
(6) The microchip according to any one of (1) to (5), wherein the number of the input ports is one.
(7)
The microchip according to any one of (1) to (6), wherein the plurality of liquids reciprocate in the flow path.
(8) A liquid mixing method, wherein a plurality of liquids are mixed using the microchip according to any one of (1) to (7).
(9) The liquid mixing method as described in (8) above, wherein at least one kind of liquid to be mixed among the plurality of liquids is previously placed in an input port.
(10) A blood test method comprising mixing blood and a diluent using the microchip according to any one of (1) to (7) above.
(11) A flow path substrate, an input port for introducing a plurality of liquids formed on the flow path substrate, and a flow path for allowing the plurality of liquids introduced to the input port to flow while being mixed. When pressurizing the atmosphere in the flow path, pressurizing means can be connected to the input port, and the flow path has a cross-sectional area in the direction in which the liquid flows. A microchip, wherein a first channel portion larger than the first channel portion and a second channel portion having a smaller cross-sectional area than the first channel portion are alternately formed.

本発明に係るマイクロチップは、投入ポートに混合の対象となる複数の液体を入れ、減圧ポートに減圧手段を接続して流路内の雰囲気を加圧又は減圧することで、投入ポートに導入された複数の液体がともに流路に沿って移動する構成である。複数の液体が流路を流れる際に、断面積の小さい第２流路部から第２流路部より断面積が大きい第１流路部に流動するときには、複数の液体には乱流により、拡散する作用が生じる。また、流路に沿って第１流路部と第２流路部とを交互に連続して形成することで、この拡散作用が繰り返され、複数の液体が均一に混合することができるようになる。したがって、本発明に係るマイクロチップを使用すれば、微小量の血液と希釈液とを均一に混合することができ、血液検査方法に用いることで効率良く且つ確実に血液の混合を行うことができる。   The microchip according to the present invention is introduced into the input port by putting a plurality of liquids to be mixed into the input port and connecting the pressure reducing means to the pressure reducing port to pressurize or depressurize the atmosphere in the flow path. The plurality of liquids move along the flow path. When a plurality of liquids flow through the flow path, when flowing from the second flow path part having a small cross-sectional area to the first flow path part having a larger cross-sectional area than the second flow path part, the plurality of liquids are caused by turbulence, Diffusing action occurs. In addition, by forming the first flow path part and the second flow path part alternately and continuously along the flow path, this diffusion action is repeated so that a plurality of liquids can be mixed uniformly. Become. Therefore, if the microchip according to the present invention is used, a very small amount of blood and a diluting solution can be mixed uniformly, and blood can be mixed efficiently and reliably by using the blood test method. .

本発明によれば、粘度・比重・容量比が異なる一定量の複数の液体を簡便に混合することができるマイクロチップ、そのマイクロチップを用いた混合方法及び血液検査方法を提供できる。   According to the present invention, it is possible to provide a microchip capable of easily mixing a plurality of liquids of a certain amount having different viscosities / specific gravity / volume ratios, a mixing method using the microchip and a blood test method.

以下、本発明の実施形態を図面に基づいて詳しく説明する。
最初に、本発明に係るマイクロチップの構成を説明する。
図１に示すように、マイクロチップ１０は、流路基板１１を備えている。流路基板１１には、複数の液体を導入するための投入ポート１２と、この投入ポート１２に導入された複数の液体を混合させつつ流動させる流路１４と、流路１４に連通する減圧ポート１３とが形成されている。 Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
First, the configuration of the microchip according to the present invention will be described.
As shown in FIG. 1, the microchip 10 includes a flow path substrate 11. In the flow path substrate 11, an input port 12 for introducing a plurality of liquids, a flow path 14 for allowing the plurality of liquids introduced into the input port 12 to flow while being mixed, and a decompression port communicating with the flow path 14 13 are formed.

減圧ポート１３には、流路１４内の雰囲気を減圧する減圧手段が接続可能である。減圧手段によって流路１４内を減圧することで、予め投入ポートに導入された複数の液体がそれぞれ流路１４内を減圧ポート１３側へ流動する。   A decompression means for decompressing the atmosphere in the flow path 14 can be connected to the decompression port 13. By reducing the pressure in the flow path 14 by the pressure reducing means, a plurality of liquids introduced into the input port in advance flow in the flow path 14 toward the pressure reducing port 13.

流路１４には、液体が流動する方向（図１においてＦで示す一点鎖線の方向）に沿って第１流路部と第２流路部とが交互に形成されている。第１流路部は、流路１４において液体が流動する方向の断面積が他の流路より大きい部分ｐ２１，ｐ２２，ｐ２３，ｐ２４，ｐ２５，ｐ２６，ｐ２７，ｐ２８（以下、総称して第１流路部とする。）であり、第２流路部は、第１流路部に比べ、液体が流動する方向の断面積が小さい部分ｐ１１，ｐ１２，ｐ１３，ｐ１４，ｐ１５，ｐ１６，ｐ１７，ｐ１８，ｐ１９（以下、総称して第２流路部とする。）である。   In the flow path 14, the first flow path portions and the second flow path portions are alternately formed along the direction in which the liquid flows (the direction of the alternate long and short dash line indicated by F in FIG. 1). The first flow path portion is a portion p21, p22, p23, p24, p25, p26, p27, p28 (hereinafter collectively referred to as the first flow path) in which the cross-sectional area in the flow direction of the liquid in the flow path 14 is larger than the other flow paths. The second flow path portion is a portion p11, p12, p13, p14, p15, p16, p17, having a smaller cross-sectional area in the direction in which the liquid flows than the first flow path portion. p18, p19 (hereinafter collectively referred to as the second flow path portion).

本実施形態のマイクロチップ１０において、投入ポート１２には、液体の流動方向Ｆの沿って順に、第２流路部ｐ１１、第１流路部ｐ２１、第２流路部ｐ１２、第１流路部ｐ２２、第２流路部ｐ１３、第１流路部ｐ２３、第２流路部ｐ１４、第１流路部ｐ２４、第２流路部ｐ１５、第１流路部ｐ２５、第２流路部ｐ１６、第１流路部ｐ２６、第２流路部ｐ１７、第１流路部ｐ２７、第２流路部ｐ１８、第１流路部ｐ２８、第２流路部ｐ１９が連通している。第２流路部ｐ１９には減圧ポート１３が連通している。   In the microchip 10 of the present embodiment, the input port 12 has a second flow path part p11, a first flow path part p21, a second flow path part p12, and a first flow path in order along the liquid flow direction F. Part p22, second channel part p13, first channel part p23, second channel part p14, first channel part p24, second channel part p15, first channel part p25, second channel part p16, 1st flow path part p26, 2nd flow path part p17, 1st flow path part p27, 2nd flow path part p18, 1st flow path part p28, 2nd flow path part p19 are connected. The decompression port 13 communicates with the second flow path part p19.

流路１４に形成する第１流路部と第２流路部のそれぞれの数は特に限定されないが、少なくとも１つの第２流路部と、該第２流路部に対して流動方向Ｆの前後に第１流路部が設けられていることが好ましい。   The number of each of the first flow path portions and the second flow path portions formed in the flow path 14 is not particularly limited, but at least one second flow path portion and the flow direction F with respect to the second flow path portion. It is preferable that the 1st flow path part is provided before and behind.

本実施形態において、流路１４は投入ポート１２から減圧ポート１３に向かう方向（図１中矢印ｙ方向）に対して垂直な方向（図１中矢印ｘ方向）に迂回するように、流路基板の平面視において略波状に形成されている。しかし、流路１４の形状はこれに限定されず、第１流路部と第２流路部とを交互に形成することができる範囲において適宜変更することができる。   In the present embodiment, the flow path substrate 14 is detoured in a direction (arrow x direction in FIG. 1) perpendicular to the direction (arrow y direction in FIG. 1) from the input port 12 toward the decompression port 13. In the plan view of FIG. However, the shape of the flow path 14 is not limited to this, and can be appropriately changed within a range in which the first flow path portions and the second flow path portions can be alternately formed.

次に、本発明に係るマイクロチップ１０の製造方法の一例を説明する。
マイクロチップ１０は、プレート表面上にマイクロドリルで流路基板を加工して製作される。流路基板１１の材料は無機材質でも良いし、有機材質でもいい。流路基板１１に使用される無機材質の例を挙げれば金属、シリコン、テフロン（登録商標）、ガラス、セラミックスなどである。有機材質はプラスチック、ゴムなどである。 Next, an example of a method for manufacturing the microchip 10 according to the present invention will be described.
The microchip 10 is manufactured by processing a flow path substrate on a plate surface with a micro drill. The material of the flow path substrate 11 may be an inorganic material or an organic material. Examples of inorganic materials used for the flow path substrate 11 are metal, silicon, Teflon (registered trademark), glass, ceramics, and the like. Organic materials include plastic and rubber.

ここで、プラスチックの例としては、ＣＯＰ、ＰＳ、ＰＣ、ＰＭＭＡ、ＰＥ、ＰＥＴ、ＰＰ等を挙げることができる。ゴムの例としては、天然ゴム、合成ゴム、シリコンゴム、ＰＤＭＳ（polydimethylsiloxane）等を挙げることができる。シリコン含有物質としては、ガラス、石英、シリコンウエファー等のアモルファスシリコン、ポリメチルシロキサンなどのシリコーンが挙げられる。   Here, examples of the plastic include COP, PS, PC, PMMA, PE, PET, PP, and the like. Examples of rubber include natural rubber, synthetic rubber, silicon rubber, PDMS (polydimethylsiloxane) and the like. Examples of the silicon-containing substance include amorphous silicon such as glass, quartz, and silicon wafer, and silicone such as polymethylsiloxane.

特に好ましい例としては、ＰＭＭＡ、ＣＯＰ、ＰＳ、ＰＣ、ＰＥＴ、ＰＤＭＳ、ガラス、シリコンウエファー等を挙げることができる。   Particularly preferred examples include PMMA, COP, PS, PC, PET, PDMS, glass, silicon wafer and the like.

流路１４の形状については、細い部分は特に限定はないが、直線状、曲線状など、いずれの形態をとることも可能であるが、直線状であることが好ましい。第１流路部の太い拡張部分は六角形、円形、四角形、多角形が望ましい。更に望ましくは六角形である。こうすることで、流動させる液体同士の拡散の作用が生じやすくなる。液の流動性を良くするために多角形の角部はＲ形状にすることが望ましい。   The shape of the flow path 14 is not particularly limited as to the thin portion, but it can take any form such as a straight line or a curved line, but is preferably a straight line. The thick expanded portion of the first flow path is preferably a hexagon, a circle, a rectangle, or a polygon. More preferably, it is a hexagon. By doing so, the effect of diffusion between the fluids that flow is likely to occur. In order to improve the fluidity of the liquid, it is desirable that the corners of the polygon have an R shape.

第２流路部における細い部分流路の幅は必要に応じて適宜広くすることも狭くすることもできる。検体量が少ない場合は、マイクロ流路であることが望ましい。マイクロ流路は、本明細書において、等価直径３ｍｍ以下の流路を言う。   The width of the narrow partial flow path in the second flow path portion can be appropriately increased or decreased as necessary. When the amount of specimen is small, it is desirable to use a microchannel. In the present specification, the micro channel refers to a channel having an equivalent diameter of 3 mm or less.

本発明でいう等価直径（equivalent diameter）は、相当(直)径とも呼ばれ、機械工学の分野で一般的に用いられている用語である。任意断面形状の配管(本発明では流路に当たる。)に対し等価な円管を想定するとき、その等価円管の直径を等価直径といい、ｄｅｑ：等価直径は、Ａ:配管の断面積、ｐ:配管のぬれぶち長さ(周長)を用いて、ｄｅｑ＝４Ａ／ｐと定義される。円管に適用した場合、この等価直径は円管直径に一致する。等価直径は等価円管のデータを基に、その配管の流動あるいは熱伝達特性を推定するのに用いられ、現象の空間的スケール（代表的長さ）を表す。等価直径は、一辺ａの正四角形管ではｄｅｑ＝４ａ2／４ａ＝ａ、路高さｈの平行平板間の流れではｄｅｑ＝２ｈとなる。これらの詳細は「機械工学事典」（（社）日本機械学会編１９９７年、丸善（株））に記載されている。 The equivalent diameter referred to in the present invention is also called an equivalent diameter and is a term generally used in the field of mechanical engineering. When an equivalent circular pipe is assumed for a pipe having an arbitrary cross-sectional shape (which corresponds to a flow path in the present invention), the diameter of the equivalent circular pipe is referred to as an equivalent diameter, deg: equivalent diameter is A: cross-sectional area of the pipe, p: Def = 4 A / p is defined using the wetted length (peripheral length) of the pipe. When applied to a circular tube, this equivalent diameter corresponds to the circular tube diameter. The equivalent diameter is used to estimate the flow or heat transfer characteristics of the pipe based on the data of the equivalent circular pipe, and represents the spatial scale (typical length) of the phenomenon. The equivalent diameter is deq = 4a 2 / 4a = a for a regular square tube with one side a, and deq = 2h for a flow between parallel flat plates with a path height h. Details of these are described in “Mechanical Engineering Dictionary” (edited by the Japan Society of Mechanical Engineers, 1997, Maruzen Co., Ltd.).

本発明に用いられるマイクロ流路の等価直径は３ｍｍ以下であるが、好ましくは１０〜2000μｍであり、特に好ましくは２０〜1000μｍである。   The equivalent diameter of the microchannel used in the present invention is 3 mm or less, preferably 10 to 2000 μm, particularly preferably 20 to 1000 μm.

また流路１４の長さには特に制限はないが、好ましくは１ｍｍ〜１００００ｍｍであり、特に好ましくは2ｍｍ〜１００ｍｍである。   The length of the flow path 14 is not particularly limited, but is preferably 1 mm to 10000 mm, and particularly preferably 2 mm to 100 mm.

本発明に用いられる流路１４の幅は、１〜３０００μｍであることが好ましく、より好ましくは１０〜２０００μｍであり、さらに好ましくは５０〜１０００μｍ である。流路１４の幅が上記範囲であると、血液などの検体が、流路１４の壁から抵抗を受けて流動性が低下することが少なく、かつ、検体の量を少量にとどめることが できるため、好ましい。   The width of the flow path 14 used in the present invention is preferably 1 to 3000 μm, more preferably 10 to 2000 μm, and still more preferably 50 to 1000 μm. When the width of the flow channel 14 is in the above range, a sample such as blood is less likely to receive resistance from the wall of the flow channel 14 and the fluidity is reduced, and the amount of the sample can be kept small. ,preferable.

第１流路部の、液体の流動方向Ｆに対して垂直な断面積が、第２の流路部の断面積に対して２倍以上であることが好ましく、より好ましくは３倍以上である。また、第１流路部の容積が複数の液体全体の体積の８０％以上であることが好ましい。   The cross-sectional area perpendicular to the liquid flow direction F of the first flow path part is preferably at least twice, more preferably at least three times the cross-sectional area of the second flow path part. . Moreover, it is preferable that the volume of the 1st flow path part is 80% or more of the volume of the whole some liquid.

第１流路部における液体の流れる方向に平行な方向の長さが、第２流路部における液体の流れる方向に平行な方向の長さに対して０．１〜１０倍であることが好ましい。   It is preferable that the length of the first flow path portion in the direction parallel to the liquid flow direction is 0.1 to 10 times the length of the second flow path portion in the direction parallel to the liquid flow direction. .

流路１４には、第１流路部と第２流路部が交互に連続して複数個存在し、その数が１〜１００個であることが望ましく、より好ましくは３〜５０個であり、さらに好ましくは５〜１５個である。   In the flow path 14, there are a plurality of first flow path portions and second flow path portions alternately and continuously, and the number is desirably 1 to 100, more preferably 3 to 50. More preferably, it is 5-15.

また、液体の混合方式は混合流路に沿って、一つの方向でもいいし、往復しても良い。   Further, the liquid mixing method may be one direction or reciprocating along the mixing channel.

流路１４の内部表面に親、疎水化処理を施すことが好ましい。水性検体の場合は親水化処理、油性検体の場合、疎水化処理が必要である。親疎水化処理法として、従来の表面処理方法が適用できる。大きく分けて、化学的表面処理法と物理的表面処理法がある。化学的表面処理法としては、薬品処理、カップリング剤による処理、蒸気処理、グラフト化、電気化学的方法、添加剤による表面改質などがある。物理的表面処理法としては、UV照射、電子線処理、イオンビーム照射、低温プラズマ処理、CASING処理、グロー、コロナ放電処理、酸素プラズマなどの方法がある。   The inner surface of the flow path 14 is preferably subjected to a parent / hydrophobic treatment. Hydrophilic treatment is required for aqueous samples, and hydrophobic treatment is required for oily samples. A conventional surface treatment method can be applied as the hydrophilic / hydrophobic treatment method. Broadly divided, there are chemical surface treatment methods and physical surface treatment methods. Chemical surface treatment methods include chemical treatment, treatment with a coupling agent, steam treatment, grafting, electrochemical methods, and surface modification with additives. Examples of physical surface treatment methods include UV irradiation, electron beam treatment, ion beam irradiation, low temperature plasma treatment, CASING treatment, glow, corona discharge treatment, and oxygen plasma.

次に、血液と希釈液を混合する手順は図面を参照して説明する。図２は、マイクロチップで２種の液体（ここでは、血液と希釈液）を混合する手順を説明する図である。
先ず、導入ポート１２にピペットを用いて0.5μLの血液Ｌ１と25μLの希釈液Ｌ２を入れ、減圧ポート１３に接続された減圧装置（例えばシリンジポンプ）により、流路の減圧を開始する。又は、導入ポート１２に加圧装置（加圧手段）を接続して、流路内部を加圧してもいい。さらに、流路内を血液Ｌ１と希釈液Ｌ２とが往復移動する方式であってもよい。 Next, the procedure for mixing blood and diluent will be described with reference to the drawings. FIG. 2 is a diagram illustrating a procedure for mixing two kinds of liquids (here, blood and diluent) with a microchip.
First, 0.5 μL of blood L1 and 25 μL of diluent L2 are introduced into the introduction port 12 using a pipette, and the pressure reduction of the flow path is started by a pressure reduction device (for example, a syringe pump) connected to the pressure reduction port 13. Alternatively, a pressure device (pressurizing means) may be connected to the introduction port 12 to pressurize the inside of the flow path. Furthermore, a system in which the blood L1 and the diluent L2 reciprocate in the flow path may be used.

減圧を開始すると、図２（ａ）に示すように、比重・粘度が低い希釈液Ｌ２が先に流路１４内に導かれ、次に血液Ｌ１が流路内に導かれる。流路１４の断面積の拡縮がない場合はこのまま混ざり合うことはない。   When decompression is started, as shown in FIG. 2A, the diluent L2 having a low specific gravity / viscosity is first introduced into the flow path 14, and then the blood L1 is guided into the flow path. When there is no expansion / contraction of the cross-sectional area of the flow path 14, it does not mix as it is.

第２流路部ｐ１１を経由して第1流路部ｐ２１に流動した希釈液Ｌ２が、該第２流路部ｐ１１から第1流路部ｐ２１に至る流路１４内部の空間の拡張に応じ、第1流路部ｐ２１において拡散され、続いて、血液Ｌ１が第1流路部ｐ２１において同様に拡散される。こうして、血液Ｌ１と希釈液Ｌ２には、ともに拡散の作用が働き、血液Ｌ１と希釈液Ｌ２とが互いに混合される（図２（ｂ）参照）。以下、血液Ｌ１と希釈液Ｌ２との混合液をＬ３とする。   The diluent L2 that has flowed to the first flow path part p21 via the second flow path part p11 corresponds to the expansion of the space inside the flow path 14 from the second flow path part p11 to the first flow path part p21. Then, it is diffused in the first flow path part p21, and then the blood L1 is similarly diffused in the first flow path part p21. Thus, the blood L1 and the diluent L2 both have a diffusion action, and the blood L1 and the diluent L2 are mixed with each other (see FIG. 2B). Hereinafter, a mixed solution of blood L1 and diluent L2 is referred to as L3.

次に、図２（ｃ）に示すように、第２流路部ｐ１２から第１流路部ｐ２２に混合液Ｌ３が流動する際に、再び混合液Ｌ３に拡散する作用が働き、第１流路部ｐ２２において更に血液Ｌ１と希釈液Ｌ２とが混合される。   Next, as shown in FIG. 2 (c), when the mixed liquid L3 flows from the second flow path part p12 to the first flow path part p22, the action of diffusing again into the mixed liquid L3 works. In the path portion p22, the blood L1 and the diluent L2 are further mixed.

図２（ｄ）から（ｅ）に示すように、混合液Ｌ３が第１流路部及び第２流路部を交互に流動することで、血液Ｌ１と希釈液Ｌ２とが次第に混合される。   As shown in FIGS. 2D to 2E, the mixed liquid L3 alternately flows through the first flow path section and the second flow path section, so that the blood L1 and the diluent L2 are gradually mixed.

ここで、複数の液体を効率的に混合するために、断面積の大きい部分である第１流路部の容積は、混合する２液の容積の合計と概略等しいかそれより大きいことが望ましい。３種類以上の液体を投入する場合には混合する複数の液体の容積の合計と概略等しいかそれより大きいことが望ましい。   Here, in order to efficiently mix a plurality of liquids, it is desirable that the volume of the first flow path portion, which is a portion having a large cross-sectional area, be approximately equal to or larger than the total volume of the two liquids to be mixed. When three or more kinds of liquids are charged, it is desirable that the total volume of a plurality of liquids to be mixed is approximately equal to or larger than the sum.

マイクロドリルで流路を作成する場合には流路１４の深さは一定で製作するのが効率的であり、この場合、流路１４の断面積の拡縮は流路１４の幅寸法（流路基板１１の平面視において流動方向Ｆに対して垂直な方向の寸法Ｄ，ｄ）の拡縮によって行う。送液に伴う液切れ、気泡混入を防ぐために断面積の拡縮は徐々に行うことが望ましく、角部はＲ形状であることが望ましい。流路幅によって拡縮を行う場合拡縮部形状は三角形状であり、広がり角度（図１の角度Ａ）が90°以下であることが望ましい。   When creating a flow path with a micro drill, it is efficient to manufacture the flow path 14 with a constant depth. In this case, the expansion and contraction of the cross-sectional area of the flow path 14 is the width dimension of the flow path 14 (flow path This is performed by expanding and contracting the dimensions D and d) in the direction perpendicular to the flow direction F in the plan view of the substrate 11. In order to prevent liquid breakage and bubble mixing due to liquid feeding, it is desirable to gradually expand and contract the cross-sectional area, and it is desirable that the corners have an R shape. In the case of performing expansion / contraction depending on the flow path width, the expansion / contraction portion shape is triangular, and the expansion angle (angle A in FIG. 1) is desirably 90 ° or less.

また、流路途中の液残りを最小限にするために、流路１４の底面の角部はR形状にすることが望ましい。R寸法は流路幅の1/10〜1/2が適当である。   Further, in order to minimize the liquid remaining in the middle of the flow path, it is desirable that the corner of the bottom surface of the flow path 14 has an R shape. The R dimension is suitably 1/10 to 1/2 of the channel width.

以下に、実施例、比較例を挙げて本発明を詳しく説明する。こ本発明はこれらの実施例にのみ限定されるものではない。   Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples. The present invention is not limited to these examples.

（実施例1：混合流路の作成）
樹脂プレート表面上にマイクロドリルで流路基板を加工した（図1）。その後、同サイズのPDMSプレートと一緒にプラズマ親水化15分処理した。PDMSプレートを流路基板上に装着し、PDMSの自己吸着力により流路の密閉状態を作り、混合用流路完成した。PDMSプレイトには、被混合液の導入ポートと減圧手段接続部（減圧ポート）に適切な大きさの孔が開いている。 (Example 1: Creation of mixing channel)
The flow path substrate was processed on the surface of the resin plate with a micro drill (Fig. 1). Thereafter, plasma hydrophilization was performed for 15 minutes together with a PDMS plate of the same size. A PDMS plate was mounted on the channel substrate, and the channel was sealed by the self-adsorptive power of PDMS, completing the mixing channel. In the PDMS plate, a hole of an appropriate size is opened at the introduction port of the liquid mixture and the decompression means connecting portion (decompression port).

（実施例２：混合効果の確認）
実施例１に作製した流路を用い性質の異なる2液の混合実験を行った。
ピペットにより、被混合液の導入ポートに血液0.5μLと希釈液25μLを入れ、PDMSの減圧手段接続部に接続された減圧装置（例えばシリンジポンプ）により、流路の減圧を開始する。 (Example 2: Confirmation of mixing effect)
A mixing experiment of two liquids having different properties was performed using the flow path prepared in Example 1.
Using a pipette, 0.5 μL of blood and 25 μL of diluent are introduced into the mixed solution introduction port, and the pressure reduction of the flow path is started by a pressure reducing device (for example, a syringe pump) connected to the pressure reducing means connecting portion of the PDMS.

減圧を開始すると、比重・粘度が低い希釈液が先に流路内に導かれ、次に血液が流路内に導かれる。流路断面積の拡張により液の拡散効果があり、数回繰り返しによって、次第に２液が混合されていく。   When decompression is started, a diluent having a low specific gravity / viscosity is first introduced into the channel, and then blood is introduced into the channel. The expansion of the channel cross-sectional area has a liquid diffusing effect, and the two liquids are gradually mixed by repeating several times.

血液と希釈液均一に混合された様子は写真で確認できた。同時に分光光度計（ＭＣＰＤ-2000（大塚電子））を用いて、図２（ｆ）に示すように、中心波長510nmの可視光でセル中のＴａ,Ｔｂ,Ｔｃの３箇所の透過光学濃度を測定した。３箇所それぞれのOD値がまったく一致であるので、血液と希釈液が均一に混合されることがわかった。   It was confirmed by photography that the blood and the diluted solution were mixed uniformly. At the same time, using a spectrophotometer (MCPD-2000 (Otsuka Electronics Co., Ltd.)), as shown in FIG. 2 (f), the transmission optical densities at three locations of Ta, Tb, and Tc in the cell with visible light having a central wavelength of 510 nm were It was measured. Since the OD values at the three locations were exactly the same, it was found that the blood and the diluent were mixed uniformly.

（実施例３：HbA1cの検出）
特開平８−１２２３３５号公報に記載の実施例2と同様の方法で、ヘモグロビンＡ1c用多層乾式スライドを作製した。このスライドに、既知量のヒトＨｂＡ1Cを含有するpH7の50mMグリセロ燐酸緩衝溶液10μLを点着し、37℃に保って、分光光度計（ＭＣＰＤ-2000（大塚電子））でＰＥＴ支持体側から中心波長650nmの可視光で反射光学濃度を測定した。点着から３分後および５分後の反射光学濃度の差（ΔＯＤ５-３）を求めて、検量線を作成した。図３に示すように、ヘモグロビンＡ1c分析用乾式免疫分析要素はヘモグロビンＡ1Cの定量を精度良く行えることが明らかである。 (Example 3: Detection of HbA1c)
A multilayer dry slide for hemoglobin A1c was prepared in the same manner as in Example 2 described in JP-A-8-122335. On this slide, 10 μL of a pH 7 50 mM glycerophosphate buffer solution containing a known amount of human HbA1C was spotted, and kept at 37 ° C. with a spectrophotometer (MCPD-2000 (Otsuka Electronics)) from the PET support side to the center wavelength. The reflection optical density was measured with visible light of 650 nm. A calibration curve was prepared by calculating the difference in reflection optical density (ΔOD 5-3 ) 3 minutes and 5 minutes after the spotting. As shown in FIG. 3, it is clear that the dry immunoassay element for hemoglobin A 1c analysis can accurately quantify hemoglobin A 1C.

全血0.5μLを混合液導入ポート（希釈液25μLを事前入れ）に入れ、PDMSの減圧手段接続部に接続された減圧装置（例えばシリンジポンプ）により、液を動かし、混合後の検体液を一定量で反応検出部のヘモグロビンＡ1c用多層乾式スライドに導入して、37℃に保って、分光光度計（ＭＣＰＤ-2000（大塚電子））でＰＥＴ支持体側から中心波長650nmの可視光で反射光学濃度を測定した。点着から３分後および５分後の反射光学濃度の差（ΔＯＤ５-３）を求めて、検量線からヘモグロビンＡ1Cの量を求める（測定回数、Ｎ＝5）。ヘモグロビンＡ1Cの測定値 (g/dL)は1.07±0.04であり、CVは3.7％であった。 Place 0.5 μL of whole blood into the mixed solution introduction port (25 μL of diluted solution in advance), move the solution with a decompression device (for example, syringe pump) connected to the decompression means connection part of PDMS, and keep the mixed sample solution constant Introduced into a multilayer dry slide for hemoglobin A1c in the reaction detection unit in an amount, kept at 37 ° C., and reflected optical density with visible light with a center wavelength of 650 nm from the PET support side with a spectrophotometer (MCPD-2000 (Otsuka Electronics)) Was measured. The difference in reflection optical density (ΔOD 5-3 ) 3 minutes and 5 minutes after the spotting is obtained, and the amount of hemoglobin A1C is obtained from the calibration curve (number of measurements, N = 5). The measured value (g / dL) of hemoglobin A1C was 1.07 ± 0.04, and the CV was 3.7%.

比較例として、同じ血液サンプルと希釈溶血液をチップ外でピペット吸引による完全混合溶血後、同じ量でヘモグロビンＡ1c用多層乾式スライドに供給し、37℃に保って、分光光度計（ＭＣＰＤ-2000（大塚電子））でＰＥＴ支持体側から中心波長650nmの可視光で反射光学濃度を測定した。点着から３分後および５分後の反射光学濃度の差（ΔＯＤ５-３）を求めて、検量線からヘモグロビンＡ1Cの量を求める（測定回数、Ｎ＝5）。ヘモグロビンＡ1Cの測定値 (g/dL) は1.06±0.035、CVは3.3％。この混合チップによる混合効果は従来の攪拌方法とほぼ同じ効果を得られた。 As a comparative example, the same blood sample and diluted hemolyzed blood were completely mixed and hemolyzed by pipette suction outside the chip, then supplied in the same amount to a multilayer dry slide for hemoglobin A1c, kept at 37 ° C., and spectrophotometer (MCPD-2000 ( Otsuka Electronics)) measured the reflection optical density with visible light having a center wavelength of 650 nm from the PET support side. The difference in reflection optical density (ΔOD 5-3 ) 3 minutes and 5 minutes after the spotting is obtained, and the amount of hemoglobin A1C is obtained from the calibration curve (number of measurements, N = 5). The measured value (g / dL) of hemoglobin A1C is 1.06 ± 0.035, CV is 3.3%. The mixing effect by this mixing chip was almost the same as the conventional stirring method.

（実施例４：CRPの検出）
特開2003-75445号公報に記載の実施例と同様の方法で、CRP用多層乾式スライドを作製した。このスライドに、既知量のヒトCRPを含有するpH7の50mMグリセロ燐酸緩衝溶液10μLを点着し、37℃に保って、分光光度計（ＭＣＰＤ-2000（大塚電子））でＰＥＴ支持体側から中心波長650nmの可視光で反射光学濃度を測定した。点着から３分後および５分後の反射光学濃度の差（ΔＯＤ５-３）を求めて、検量線を作成した。図４に示すように、CRP分析用乾式免疫分析要素はCRPの定量を精度良く行えることが明らかである。 (Example 4: CRP detection)
A multilayer dry slide for CRP was produced in the same manner as in the examples described in JP-A-2003-75445. This slide is spotted with 10 μL of a pH 7 50 mM glycerophosphate buffer solution containing a known amount of human CRP, kept at 37 ° C., and center wavelength from the PET support side with a spectrophotometer (MCPD-2000 (Otsuka Electronics)). The reflection optical density was measured with visible light of 650 nm. A calibration curve was prepared by calculating the difference in reflection optical density (ΔOD 5-3 ) 3 minutes and 5 minutes after the spotting. As shown in FIG. 4, it is clear that the dry immunoassay element for CRP analysis can accurately quantify CRP.

ＣＲＰ濃度が既知のＣＲＰ標準血清1μLを混合液導入ポート（希釈液20μLを事前入れ）に入れ、PDMSの減圧手段接続部に接続された減圧装置（例えばシリンジポンプ）により、液を動かし、混合後の検体液を10μLで反応検出部のCRP用多層乾式スライドに導入して、37℃に保って、分光光度計（ＭＣＰＤ-2000（大塚電子））でＰＥＴ支持体側から中心波長650nmの可視光で反射光学濃度を測定した。点着から３分後および５分後の反射光学濃度の差（ΔＯＤ５-３）を求めて、検量線からCRPの量を求める（測定回数、Ｎ＝5）。この結果、CRPの測定値 (g/dL)が3.00±0.08であり、CVが2.7％であった。 Put 1 μL of CRP standard serum with known CRP concentration into the mixture introduction port (pre-fill with 20 μL of diluent), move the solution with a decompression device (eg syringe pump) connected to the PDMS decompression means connection, and after mixing 10 μL of the sample solution was introduced into a multilayer dry slide for CRP in the reaction detection unit, kept at 37 ° C., and visible light with a center wavelength of 650 nm from the PET support side with a spectrophotometer (MCPD-2000 (Otsuka Electronics)). The reflection optical density was measured. The difference in reflection optical density (ΔOD 5-3 ) 3 minutes and 5 minutes after the spotting is determined, and the amount of CRP is determined from the calibration curve (number of measurements, N = 5). As a result, the measured value (g / dL) of CRP was 3.00 ± 0.08, and CV was 2.7%.

比較例として、同じサンプルと希釈液をチップ外でピペット吸引による完全混合後、同じ量でCRP用多層乾式スライドに供給し、37℃に保って、分光光度計（ＭＣＰＤ-2000（大塚電子））でＰＥＴ支持体側から中心波長650nmの可視光で反射光学濃度を測定した。点着から3分後および5分後の反射光学濃度の差（ΔＯＤ5-3）を求めて、検量線からCRPの量を求める（測定回数、Ｎ＝5）。この結果、CRPの測定値 (g/dL)が3.06±0.1であり、CVが3.2％であった。 As a comparative example, the same sample and diluent are thoroughly mixed by pipette suction outside the tip, then supplied in the same amount to a multilayer dry slide for CRP, kept at 37 ° C, and a spectrophotometer (MCPD-2000 (Otsuka Electronics)) The reflection optical density was measured with visible light having a center wavelength of 650 nm from the PET support side. The difference in reflection optical density (ΔOD 5-3 ) 3 minutes and 5 minutes after the spotting is obtained, and the amount of CRP is obtained from the calibration curve (number of measurements, N = 5). As a result, the measured value (g / dL) of CRP was 3.06 ± 0.1, and CV was 3.2%.

（実施例５：アルデヒド脱水素酵素遺伝子（ＡＬＤＨ２）の検出）
特開2003-61658号に記載の実施例と同様の方法で、増幅検出用ピロリン酸多層乾式スライドを作製した。下記に示す反応液５０μLを導入ポートに事前に入れ、精製されたヒトＤＮＡ試料１μＬを、参照用として蒸留水１μＬを混合液導入ポートに入れた。そして、PDMSの減圧手段接続部に接続された減圧装置（例えばシリンジポンプ）により、温度サイクル部位に液を動かす。 (Example 5: Detection of aldehyde dehydrogenase gene (ALDH2))
A pyrophosphoric acid multilayer dry slide for amplification detection was prepared in the same manner as in the examples described in JP-A-2003-61658. 50 μL of the reaction solution shown below was placed in advance in the introduction port, 1 μL of the purified human DNA sample was placed in the mixture introduction port and 1 μL of distilled water was used as a reference. And a liquid is moved to a temperature cycle site | part by the decompression device (for example, syringe pump) connected to the decompression means connection part of PDMS.

１０×ＰＣＲバッファー ５μＬ
２．５ｍＭ ｄＮＴＰ ５μＬ
５μＭフ゜ライマー１ ２μＬ
５μＭフ゜ライマー２ ２μＬ
Tag １μＬ
精製水 ３５μＬ 10 × PCR buffer 5 μL
2.5 mM dNTP 5 μL
5 μM primer 12 μL
5 μM primer 2 2 μL
Tag 1μL
Purified water 35μL

プライマー１
5-AACGAAGCCCAGCAAATGA-3
プライマー２
5-GGGCTGCAGGCATACACAGA-3 Primer 1
5-AACGAAGCCCAGCAAATGA-3
Primer 2
5-GGGCTGCAGGCATACACAGA-3

本測定では、デネイチャーを９４℃で２０秒行い、アニーリングを６０℃で３０秒行った。また、ポリメラーゼ伸長反応を７２℃で１分３０秒施す工程を３５サイクル繰り返すことでＰＣＲ増幅を実施した。さらに、ＰＣＲ増幅実施後の液を、増幅検出用ピロリン酸多層乾式スライドに導入して37℃に保って、分光光度計（ＭＣＰＤ-2000（大塚電子））でＰＥＴ支持体側から中心波長650nmの可視光で５分後の反射光学濃度を測定した。   In this measurement, denaturing was performed at 94 ° C. for 20 seconds, and annealing was performed at 60 ° C. for 30 seconds. In addition, PCR amplification was performed by repeating the cycle of applying the polymerase extension reaction at 72 ° C. for 1 minute 30 seconds for 35 cycles. Furthermore, the solution after PCR amplification was introduced into a pyrophosphate multi-layer dry slide for amplification detection and maintained at 37 ° C., and visible with a spectrophotometer (MCPD-2000 (Otsuka Electronics)) at a center wavelength of 650 nm from the PET support side. The reflection optical density after 5 minutes was measured with light.

以下、点着から５分後の反射光学濃度を示す。
ＤＮＡ試料 ０．５４８
蒸留水 ０．３２２ Hereinafter, the reflection optical density after 5 minutes from the spotting is shown.
DNA sample 0.548
Distilled water 0.322

このように、ＤＮＡ試料の光学濃度が蒸留水の光学濃度よりも高いことから、ＡＬＤＨ遺伝子が検出することができることが分かる。   Thus, it can be seen that the ALDH gene can be detected because the optical density of the DNA sample is higher than the optical density of distilled water.

本発明に係るマイクロチップの構成図である。It is a block diagram of the microchip based on this invention. マイクロチップを用いて血液及び希釈液の混合を行う工程を示す図である。It is a figure which shows the process of mixing blood and diluent using a microchip. グリコヘモグロビン測定用分析要素の検量線を示すグラフである。It is a graph which shows the calibration curve of the analysis element for glycohemoglobin measurement. ＣＲＰ乾式分析要素の検量線を示すグラフである。It is a graph which shows the calibration curve of a CRP dry analytical element.

符号の説明Explanation of symbols

１０ マイクロチップ
１１ 流路基板
１２ 投入ポート
１３ 減圧ポート
１４ 流路
ｐ１１〜ｐ１９ 第２流路部
ｐ２１〜ｐ２８ 第１流路部 10 Microchip 11 Flow path substrate 12 Input port 13 Decompression port 14 Flow path p11 to p19 Second flow path part p21 to p28 First flow path part

Claims (11)

流路基板と、
前記流路基板に形成され、複数の液体を導入するための投入ポートと、
前記投入ポートに導入された前記複数の液体を混合させつつ流動させる流路と、
前記流路に連通し、該流路内の雰囲気を減圧する際に、減圧手段が接続可能な減圧ポートとを備え、
前記流路には、前記液体が流動する方向の断面積が他の流路における断面積に比して大きい第１流路部と、前記第１流路部より断面積が小さい第２流路部とが交互に形成されていることを特徴とするマイクロチップ。 A flow path substrate;
An input port for introducing a plurality of liquids formed on the flow path substrate;
A flow path for flowing while mixing the plurality of liquids introduced into the charging port;
A pressure reducing port that communicates with the flow path and is connectable to a pressure reducing means when the atmosphere in the flow path is reduced.
The flow path includes a first flow path portion in which a cross-sectional area in a direction in which the liquid flows is larger than cross-sectional areas in other flow paths, and a second flow path having a smaller cross-sectional area than the first flow path portion. A microchip characterized in that the portions are alternately formed. 前記第１流路部の断面積が前記第２の流路部の断面積に対して２倍以上であることを特徴とする請求項１に記載のマイクロチップ。   2. The microchip according to claim 1, wherein a cross-sectional area of the first flow path portion is twice or more a cross-sectional area of the second flow path portion. 前記第１流路部の容積が前記複数の液体全体の体積の８０％以上であることを特徴とする請求項１又は２に記載のマイクロチップ。   3. The microchip according to claim 1, wherein a volume of the first flow path portion is 80% or more of a volume of the whole of the plurality of liquids. 前記第１流路部における前記液体の流れる方向に平行な方向の長さが、前記第２流路部における前記液体の流れる方向に平行な方向の長さに対して０．１〜１０倍であることを特徴とする請求項１から３のいずれか１つに記載のマイクロチップ。   The length of the first flow path portion in the direction parallel to the liquid flow direction is 0.1 to 10 times the length of the second flow path portion in the direction parallel to the liquid flow direction. The microchip according to claim 1, wherein the microchip is provided. 前記流路の底面の角部が流路幅の１０％以上の曲率半径を有することを特徴とする請求項１から４のいずれか１つに記載のマイクロチップ。   5. The microchip according to claim 1, wherein a corner portion of a bottom surface of the flow path has a curvature radius of 10% or more of a flow path width. 前記投入ポートが１つであることを特徴とする請求項１から５のいずれか１つに記載のマイクロチップ。   6. The microchip according to claim 1, wherein the number of the input ports is one. 前記複数の液体が前記流路を往復移動することを特徴とする請求項１から６のいずれか１つに記載のマイクロチップ。   The microchip according to any one of claims 1 to 6, wherein the plurality of liquids reciprocate in the flow path. 上記請求項１から７のいずれか１つに記載のマイクロチップを用いて複数の液体を混合することを特徴とする液体の混合方法。   A liquid mixing method comprising mixing a plurality of liquids using the microchip according to any one of claims 1 to 7. 前記複数の液体のうち少なくとも１種類の被混合液を投入ポートに予め入れておくことを特徴とする請求項８に記載の液体の混合方法。   9. The liquid mixing method according to claim 8, wherein at least one kind of liquid to be mixed among the plurality of liquids is previously placed in an input port. 上記請求項１から７いずれか１つに記載のマイクロチップを用いて血液と希釈液とを混合することを特徴とする血液検査方法。   A blood test method comprising mixing blood and a diluent using the microchip according to any one of claims 1 to 7. 流路基板と、
前記流路基板に形成され、複数の液体を導入するための投入ポートと、
前記投入ポートに導入された前記複数の液体を混合させつつ流動させる流路とを備え、
前記流路内の雰囲気を加圧する際に、前記投入ポートに加圧手段が接続可能であって、
前記流路には、前記液体が流動する方向の断面積が他の流路における断面積に比して大きい第１流路部と、前記第１流路部より断面積が小さい第２流路部とが交互に形成されていることを特徴とするマイクロチップ。 A flow path substrate;
An input port for introducing a plurality of liquids formed on the flow path substrate;
A flow path for flowing while mixing the plurality of liquids introduced into the charging port,
When pressurizing the atmosphere in the flow path, a pressurizing means can be connected to the input port,
The flow path includes a first flow path portion in which a cross-sectional area in a direction in which the liquid flows is larger than cross-sectional areas in other flow paths, and a second flow path having a smaller cross-sectional area than the first flow path portion. A microchip characterized in that the portions are alternately formed.
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